DDW: Biologics Linger in Moms-to-be With IBD

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that the biologic tumor necrosis factor-alpha inhibitor adalimumab (Humira) actively, but safely, crosses the placenta in pregnant women with inflammatory bowel disease (IBD), and can be detected in neonatal serum for at least three months.

Note that the findings don't imply that women with IBD who become pregnant should stop their treatment, but that exposed infants should be monitored closely for infection and should not receive live-virus vaccines during the first six months of life.

Explain that another study suggested that the use of biologic drugs to treat IBD during pregnancy may be safe for both mother and child.

CHICAGO -- The biologic adalimumab (Humira) actively, but safely, crosses the placenta in pregnant women with inflammatory bowel disease (IBD), and can be detected in neonatal serum for at least three months, a researcher reported here.

In one series of eight women, six with Crohn's disease and two with ulcerative colitis, the drug was detected in all infants, and in every case, levels in cord blood and neonatal serum were higher than maternal levels, according to Uma Mahadevan, MD, of the University of California-San Francisco, and colleagues.

For instance, in one case the maternal level was 6.25 μg/mL, while the level in cord blood was 9.72 μg/mL and the level in neonatal blood was 6.55 μg/mL, she reported here at Digestive Disease Week.

Levels in another case were 6.05 μg/mL in the mother, 9.29 μg/mL in cord blood, and 6.17 μg/mL in the infant.

In a third instance, the respective levels were 1.84, 5.39, and 6.01 μg/mL.

Drugs such as adalimumab decrease the ability of the immune system to fight infection, as has been consistently demonstrated by increased rates of serious infection in patients with IBD, and in patients with autoimmune disorders, such as rheumatoid arthritis.

This has raised the question of whether the presence of these drugs in neonatal serum can increase the infants' risk of infection.

Follow-up of the neonates in Mahadevan's series revealed that it took four to 11 weeks for them to clear the drug from serum.

"Because of this, exposed infants should be monitored closely for infection and should not receive live-virus vaccines during the first six months of life," she said.

These findings don't imply that women with IBD who become pregnant should stop their treatment, because that would increase their chances of miscarriage, preterm birth, and low birth weight in their offspring, she said.

Both adalimumab and infliximab are IgG1 antibodies against TNF-α, and the Fc portion of IgG is actively transported across the placenta, primarily during the third trimester.

A third TNF inhibitor, certolizumab pegol (Cimzia), has a different structure and is likely to cross the placenta only passively, Mahadevan explained.

Nonetheless, all three drugs are classified as pregnancy category B, having low risk for use in pregnancy.

Mahadevan recommended giving the last dose of the TNF inhibitor around weeks 32 to 36, and although less placental transfer has been seen with certolizumab, she doesn't recommend switching pregnant women to that drug if they are already on adalimumab.

Animal studies have not shown any impact of in utero exposure on the infant's immune development, but further studies will be needed to assess this, she cautioned.

In another study presented in a poster session at the meeting, unfavorable pregnancy outcomes were higher among Spanish women with IBD treated with conventional drugs (controls), at 37%, than among those receiving the TNF inhibitors or immunomodulators such as azathioprine, at 24%.

That retrospective study, presented by Maria José Casanova, MD, of La Princesa Hospital in Madrid, and colleagues, included 202 women with IBD on the newer immune-modulating drugs and 110 controls on standard therapy.

A total of 58% of the women had Crohn's disease, and in 29% the disease was active during the pregnancy.

Unfavorable outcomes in controls and cases included:

Spontaneous abortion, 17% versus 10% (P=0.06)

Preterm delivery, 12% versus 4% (P=0.01)

Low birth weight, 10% versus 6% (P=0.2)

On multivariate analysis, treatment with immunomodulators was associated with a favorable outcome (OR 0.3, 95% CI 0.2 to 0.6) as was having Crohn's disease rather than ulcerative colitis (OR 0.5, 95% CI 0.3 to 0.9).

Use of anti-TNF drugs was not associated with an adverse outcome (OR 1.1, 95% CI 0.6 to 2.3).

These data suggest that the use of biologic drugs to treat IBD during pregnancy may be safe for both mother and child, the investigators concluded.

Mahadevan and her colleagues disclosed being on advisory committees and receiving research support from a number of companies, including Centocor, Abbott, Elan, UCB, Salix, Shire, and Bristol-Myers Squibb.

Several of Casanova's co-authors reported being on advisory committees and receiving research support from companies including AstraZeneca, Schering Plough, and Abbott.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.